Stable pharmaceutical composition of saxagliptin

Abstract

Disclosed herein is a stable pharmaceutical composition comprising a substrate having deposited on its surface a layer comprising saxagliptin or pharmaceutically acceptable salts thereof, wherein a seal coat is not present between the substrate and the saxagliptin layer.

Description

PRIORITY[0001]This application claims the benefit under 35 U.S.C. §119 to Indian Provisional Application No. 2646 / MUM / 2012, filed on Sep. 12, 2012, and to U.S. Provisional Application No. 61 / 713,322, filed on Oct. 12, 2012, the contents of each of which are incorporated by reference herein.FIELD OF INVENTION[0002]The present invention relates to a stable pharmaceutical composition comprising saxagliptin or pharmaceutically acceptable salts thereofBACKGROUND OF THE INVENTION[0003]1. Technical Field[0004]Saxagliptin is an orally-active inhibitor of the DPP4 enzyme.[0005]2. Description of the Related Art[0006]U.S. Pat. No. 7,420,079 discloses saxagliptin and its hydrochloride, trifluoroacetic acid and benzoate salts, as well as saxagliptin monohydrate. Saxagliptin is marketed under the trade name ONGLYZA® by Bristol-Myers Squibb for the treatment of type 2 diabetes.[0007]U.S. Pat. No. 6,395,767 discloses saxagliptin, (1S,3S,5S)-2-[(2S)-2-amino-2-(3-hydroxy tricyclo[3.3.1.13,7]dec-1-yl)...

AI Technical Summary

Benefits of technology

The present invention provides a stable pharmaceutical composition of saxagliptin or its pharmaceutically acceptable salt, which has no inner layer between the surface and the layer comprising saxagliptin and a pharmaceutical additive. The invention also provides a pharmaceutical composition of saxagliptin, wherein cyclic amidine impurity does not exceed 0.30% when exposed to 60°C for 7 days. The invention advantageously controls the formation of cyclic amidine impurity, even at elevated temperatures, and does not require an inner seal coat between the saxagliptin layer and the core tablet.

Problems solved by technology

Literature suggests that saxagliptin is susceptible to degradation in pharmaceutical compositions; however, very few attempts have been made to develop a stable pharmaceutical composition of saxagliptin.

U.S. Pat. No. 7,951,400 (US '400) describes saxagliptin undergoes intramolecular cyclization leading to the formation of a degradant known as cyclic amidine (mainly cis-cyclic amidine (CA)), which is therapeutically inactive thus is undesirable.

However, due to the number of coating layers, the compositions of US '400 are prove to be time consuming in terms of manufacturing at a commercial level, with the added challenge of yield optimization.